Muramyl Dipeptide (MDP, N-acetylmuramyl-L-alanyl-D-isoglutamine) is a synthetic immunoreactive peptide consisting of N-acetyl muramic acid attached to a short amino acid chain of L-Ala-D-isoGln. It was first identified in bacterial cell wall peptidoglycan as an active component in Freund's Complete Adjuvant (FCA). In 1974, MDP was discovered to be the minimal structure required for the efficacy of FCA, one of the most potent and widely used adjuvants in animal experimental models. Muramyl dipeptides are well known for their immunomodulatory properties. Muramyl dipeptides are the smallest, biologically active components of bacterial cell walls. Muramyl dipeptide derivatives have been proved to show significant immunomodulatory properties, via one of the PRRs (Pattern Recognition Receptors), nucleotide-binding oligomerization domain 2 (NOD2) receptor (Girardin S. et al., 2003. J Biol Chem. 278(11): 8869-72; F. Coulombe et al., 2012 PloS ONE, 7 (5): Article ID e36734). Muramyldipeptides activate macrophages and other cells of the immune system to kill cancer cells (I Jakopin, 2013. Current Medicinal Chemistry, 20 (16): 2068-2079; Ogawa et. al., 2011. CurrBioact Compd. 7(3): 180-197), however, it is also reported to be pyrogenic in nature. In order to reduce its pyrogenic effect, till date a series of MDP derivatives have been designed, synthesized and tested with the aim of increasing specific functions, while suppressing pyrogenicity. There are many reported inventions or publications related to synthesis of Muramyl dipeptide and its derivatives (Namba et al., 1997. Vaccine, 15(4):405-13; WO1996001645; U.S. Pat. Nos. 4,395,399; 7,173,107B2).
N-glycolyl muramyl dipeptide, GMDP (N-glycolyl glucosaminyl-N-acetylmuramyl-L-alanyl-D-isoglutamine) is one of the example of Muramyl dipeptide derivative, which was originally developed in the 1970s at the Shemyakin Institute for Bio-organic Chemistry, Moscow. GMDP has been shown to stimulate both innate and adaptive immune responses. GMDP also activates macrophages and release cytokines and colony stimulating factors (CSFs), which in turn stimulate the differentiation of hemopoietic cells to clear infections (Australasian Biotechnology, Volume 6 Number 4, July/August 1996, pp. 223-229). GMDP have been, shown to have higher immunoadjuvant activity and less pyrogenic effect, compared to MDP. Hence, several other N-acyl derivatives of MDP are more immuno-therapeutics over MDP (Andronova T. M., et al., 1991. Review. Immunology 4, 1). Hence, this molecule is been widely used in immuno-therapeutic approaches, especially to treat chronic infections, autoimmune diseases and cancer (L. I. Rostovtseva et al., 1981. Russian Journal of Bioorganic Chemistry, 7 (12): 1843-1858).
MDP-based compound Likopid™ is the first immunotherapeutic of the muramylglycopeptide type introduced to the clinical practice. Likopid™ was developed and registered by a Russian company Peptek as an immunotherapeutic with broad applicability, e.g. immunostimulation and prevention of infections complicating post-traumatic, post-operative, post-chemotherapeutic and post-radiotherapeutic patienthood. Other areas are treatment of infectious diseases, as tuberculosis, human cervical papilomavirus, ophthalmic herpetic infections, psoriasis and treatment of ulcerous and inflammation processes (WO2007045192).
Below shown structure of general Formula-X represents chemical structure of compound MDP.

There are many inventions related to Muramyl peptide compounds and its derivatives. Although, there use as therapeutic agents is known, use of MDP derivatives as adjuvants in vaccine formulations has not been documented or found at all till present.
WO1996001645 A1 relates to the use of Muramyl peptide compounds, particularly N-acetyl-D-glucosaminyl-(β1-4)-N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), for the treatment of inflammatory dermatological conditions such as psoriasis and in the treatment of immune-related diseases of the skin and mucous membranes.
U.S. Pat. No. 7,173,107B2 discloses glycopeptides and preparation thereof which is stereo-specific synthesis of a glycopeptide using a triply orthogonal protection scheme is described, in particular, the synthesis of N-acetylglucosaminyl-β-[1,4]-N-acetylmuramyl monopeptide and derivatives thereof. The glycopeptide is useful for the preparation of MDP and related compounds having a glucosaminyl-β-[1,4]-N-acetylmuramic acid disaccharide core.
WO2007045192 relates to glucosaminylmuramic acid (2-amino-2-deoxy-β-D-gluco-pyranosyl-(1→4)-N-acetylmuramic acid) derivatives, method of their synthesis, and their use for the synthesis of glucosaminylmuramylglycopeptides, i.e. disaccharide analogues of muramyl glycopeptides. U.S. Pat. No. 4,395,399 disclose different glycopeptides and their preparations.
However, despite improvements seen in several newly developed MDP derivatives, yet there is a continuous need for compounds with further reduced side-effects and increased adjuvant activity for the purpose of either therapeutic or prophylactic use in vaccine formulations. Hence it is critical to focus on the balance between efficacy and side effects, while designing or synthesizing new compounds. There is a need to develop more effective and improved MDP derivatives, which would reduce the side effects associated with known MDP derivatives. This invention describes novel MDP derivatives with reduced pyrogenicity, while maintaining a considerable effective functionality as vaccine adjuvants. In this patent application, inventors have developed and thereby disclosed new MDP derivatives, not known earlier.